Exposure of newborn mice to Gross murine leukemia virus (GMuLV) results in a highly selective and persistent infection of glial cells within the central nervous system (CNS) white matter. The majority of adult animals show no overt clinical signs of neurologic disease, virus remains localized to the initial sites of infection, and there is a selective absence of peripheral T cell immune responses to GMuLV antigens. The primary targets of GMuLV infection appear to lie within the oligodendroglial lineage, perhaps at the level of 02A glial progenitors. One consequence of this interaction is an alteration in the differentiation of these cells in vitro. In approximately 5% of animals, GMuLV infection leads to severe paralysis. Histological examination of these animals detected pockets of demyelination accompanied by mononuclear cell infiltration. Thus, GMuLV infection may trigger both direct viral and immune-mediated cytopathology. The objective of this proposal is to define the molecular parameters that regulate GMuLV tropism, with particular attention on the factors that regulate the balance between persistent infection and disease. More detailed understanding of these processes will aid in the development of therapeutic strategies for the treatment of retroviral associated CNS diseases. The specific aims of this proposal are to study: AIM 1: TROPISM OF GMuLV WITHIN THE CENTRAL NERVOUS SYSTEM AIM 2: DEVELOPMENTAL AND NEUROPATHOLOGIC CONSEQUENCES OF GMULV INFECTION AIM 3: REGULATION OF THE IMMUNE RESPONSE TO GMULV